This project consists of anatomical and biochemical studies of the neuropeptide somatostatin in mammalian retina as a model of central nervous system neuropeptide action. Because of the wodespread co-localization of somatostatin within the same forebrain neurons as neuropeptide Y and NADPH diaphorase activity, and because of the involvment of the cells containing these three markers in both Alzheimer's disease and Huntington's disease, these markers will be investigated in the retina in parallel studies. The underlying assumption is that the anatomic association of the three markers implies a functional association, and that functional connection will hold throughout the central nervous system. The studies include detailed observations of the morphology of somatostatin-, neuropeptide Y- and NADPH diaphorase-containing cells of rat, and rabbit retinas using immunocytochemistry and enzyme histochemistry. The ontogenic development of the three neuronal markers in rat retina and cerebral cortex will be studied using radioimmunoassay, chromatography, immunocytochemistry and enzyme histochemistry. Animal studies will be combined with studies of normal human retinas obtained post-mortem and retinas of patients dying with Alzheimer's disease and with Down's syndrome and Alzheimer's-like neuropathology to determine if the neurochemical abnormalities of Alzheimer's brain involve the retina as well as the brain. The mechanism of action of somatostatin will be investigated by examination of modulation of retinal adenylate cyclase activity by somatostatin. Potential interactions of somatostatin and neuropeptide Y will be of particular interest, and interactions of somatostatin and the secretin-glucagon family of peptides (including vasoactive intestinal peptide and growth hormone-releasing factor) will be sought because of their antagonistic actions in other systems. The overall goal is to investigate developmental and biochemical aspects of retinal somatostatin, neuropeptide Y and NADP diaphorase, and thereby to gain insight into the role of these markers in normal retinal function and in degenerative diseases of the nervous system.